What I (un)Learn During Internship – Part 1 (Boss Based Medicine)

Problem with medicine is its uncertainty. Everything in it keeps evolving; widen disease definition, new drugs, new diagnostic test, new surgical method, and so on. What is considered as beneficial today may be classified as harmful tomorrow. Thus, in order to prevent patients from harm of outdated medical practice, experts develop new approach in practicing medicine, Evidence Based Medicine (EBM).

I learned about it when I was in medical school. It was the module where you were taught about how to read a paper, assess validity of a trial, and find answer of clinical query. At the end of the module, I was equipped with the ability to criticize journals so that I can be more careful in seeking answers through all the available evidences.

EBM training aims to help doctors provide tailored up to date medical practice based on the latest available evidence. This skill is expected to assist doctors in their lifelong learning of medicine. So when we have graduated for 30 years long, our knowledge can still be equally up to date compared to fresh graduates. That's the dream. However, what happens in reality (as in hospital, clinic, etc, other than teaching hospital) is not as beautiful as how it should be. If teaching hospital was a city zoo, the other hospitals would be Amazon.

Internship is the first taste of real world for me and my colleagues, as fresh graduates. I captured (so many) misconducts of medicine during my first 4 months posting and the biggest problem lays in how patients diagnosed and treated.

Few weeks ago, there was a 60% burned surface patients who had been cared in ICU for 3 weeks. At that moment, she appeared to be lethargic with high temperature, high respiratory rates and high leukocyte counts. We also found some evidences of organ damage in her lab results. We were all agreed that she was in severe sepsis. In this kind of condition, there may be some beneficial use of corticosteroid.

Though its use remains controversial, but the last systematic review and meta-analysis published in JAMA on 2009 concluded beneficial effect on short term mortality outcome by low dose administration of corticosteroid. I then, suggested to her attending surgeon, the use of low dose corticosteroid to our patients.
 *Systematic review is a paper which review all other papers using clear method of inclusion and exclusion criteria while meta analysis is a study which pool all trial results, which included based on the previous systematic inclusion and exclusion, into one big spreadsheet and count the overall outcome together. Thus, systematic review and meta analysis provide strongest evidence among other type of studies.

However the attending surgeon who took care of this patient denied my idea of using corticosteroid and argued how corticosteroid would increase the severity of her condition since its effect in decreasing immune response and therefore it would make her more susceptible to infection. That sounded plausible, at first. But he didn’t aware that what actually made septic patients died was their immune reaction, instead of their infection.

Our body has the ability to defense our self from outsider such as, bacteria. When we recognize their invasion, we will automatically release our first soldiers, the innate immune system. Imagine them as cavilary soldiers with standard weapon. Later, these soldiers will call for other help, the chemoatractant (think of them as the army with radio connection which control distance weapon and control media). During all these activities, there is also undercover special forces among these armies who study the invaders tactic, known as adaptive immune system. Right after enough learning, these special forces will attack the invaders with specialized weapon according to their weakness.

If all our immune system response correctly and the bacteria is defeated, we will bnot be sick. However, sometime in special condition in which there are misresponse soldiers or too many enemies, our body will suffer from our overreacting and overactivating defense mechanism. The chemotractant will be released abundantly and therefore disrupt our body function. This is what happen in sepsis. What we need now is something to calm down our body reaction. Theoretically, corticosteroid which work in suppresing immune reaction will help our patients.

Evidence Based Medicine is designed for this kind of situation. When you are faced with life and death decision, looking through all previous trials are the only reliable ways. Unfortunately, this is where the attending surgeon is lacking. Rather than looking for evidences, he relied his judgement on basic medical knowledge.

This is what I actually find from the paper I mentioned before:

1. There is no significant different in 28 day mortality between patients administered with corticosteroid and control, RR 0.84, 95% CI 0.71-1.00; P=0.5; I2=53% in randomised trials and RR 1.05, 95% CI 0.69-1.58; P=0.83 (don’t be intimidated with these numbers, it only means that the result is not significant)
2. In the subgroup analysis, there is significant difference in 28 days mortality between patients received prolonged long term corticosteroid and control, RR 0.84, 95% CI 0.72-0.97, P=0.02 (it means that long low dose use of corticosteroid administration has significant protective effect toward septic patients).

For a dying patient, I think the result of this study is worth trying.

There are reasons why we do a lot of trials in medicine and why we practice medicine using Evidence Based Medicine approach. Our basic science of medicine is most of the time useful to help us diagnose disease but it is often misleading if we bluntly translate it into how we should manage our patients. In medicine, it is dangerous to continously feel intelligent enough or competent enough because, truthfully we can never be too smart in this field. What we thought theoretically correct are many times wrong in real practice. As mysterious as medicine can be, the wisest thing is might be to follow what the great Steve Jobs told us to do, “Stay hungry, stay foolish”. 

Science Irony

Recently, I read a few medical and science books. Two books that I read were written by Ben Goldacre, a very vocal idealist bright scientist from UK, titled Bad Science and Bad Pharma. The other book was a textbook of pharmacoepidemiology written by group of experts in the field. All of those books gather excellence evidences which criticise how we practice medicine today in term of industry interference and lost research data or inadequate drug study, though the last book doesn't say it straight forwardly.

When I read the books, I find how all of those problems in developed countries are too sophisticated and too advance to happen in my country. Problems like unpublished research data, inadequte reporting, or unnoticed long term adverse events of drugs are far beyond our ability as a country. Those problems are like fairy tale in the country where drugs are mostly still inaccessible and unaffordable. Today's most talked issue among physicians in developed countries, statin's long term side effect in geriatric patients, are somehow irrelevent with circumstances in my country where high cholesterol are still underdiagnosed and therefore undertreatment (following this sentence, I should have provided you with evidence, but there wasn't any data of how many people predicted to have high cholesterol and how many of them receive treatment. We'll talk about it later). To have such a long term side effect of expensive drug is luxurious for our people. Look how ironic this world can be.

Now let's talk about research. It's funny how Goldacre are resentful by many unpublished research data (most of them showed no significant benefit of new drugs, he's arguing that they intentionally unpublished to hide the findings thus it will favor the pharmaceutical industry), while researchers in my countries are struggling to publish their findings. Most of researchs in my country went unpublished as they were rejected by journal's editor. So that's just there hiding peacefully in the laptop. There was a moment when I was presenting my literature review on a med student championship, one of the judges, asked me why didn't I pick study from my own country while there is one Randomized Controlled Trial (RCT) that he aware had been conducted on my topic. Well, I've searched using all the available med research database, but there wasn't such study I find conducted in my country. This is a publication bias, not becuase it is unpublished but because it's insearchable. In that championsip, I decided to use a systematic review which (not so) surprisingly, doesn't contain RCT that the judge was talking about. Not even mention in the excluded studies.

According to Goldacre, many of product sellers in UK cherry picks research to back up their product selling. Cherry pick is an act where someone is selectively choose some studies which support their arguments, whereas studies can result in vary outcome. Thus, the best evidence isn't some researchs, it's a research that contains every previous studies (published or unpublished, in favor or against, significant or insignificant), it's systemmatic review and meta analysis.

In country where there are lack studies conducted in a year, and less academic journals and none of them are linked to Pubmed (biggest database of online medical studies), we have our own problem. We have data scarcity. We are unfindable. None of product sellers can cherry pick studies, which is good but devastating at the same time if we realize how lacking we are in science. We have a lot of intelligence talented scientist, some are brighters than those in developed world. However, they are forced to unscience and unsmart theirselves because of how my country treat them. There is no sufficient fund allocated for research, and if there's any only few of the research proposals selected and therefore the rest of them struglling to find their own funding, even some of them use their own fortune. Eventually, they have to choose, to stay in the country and taking regular less interesting job or to stay in the country and live as idealist scientist and live poorly or they can also choose to get out of the country and pursuing life of science abroad.

This toxic conditions leave my country in their biggest intellectual crisis. We keep arguing without evidence, we decide things without sufficient knowledge, we think we are the smartest because no one can prove we are wrong while the truth is we know nothing about our implausibility.

Reflection on Medicine

Recently, there is a new and updated version of hypertension guideline published. For over 10 years, we have used JNC VII as our approach in diagnosing and treating patients with high blood pressure. The new guideline increase its aggressiveness in starting high blood pressure treatment in some group of patients, including geriatric and comorbid patients. Though the recommendation from the panel is widen, it does not provide any significant changes in the treatment.
The new JNC VIII reminds me of a very interesting interesting research articles that I read sometime ago in PLOS, titled “Expanding Disease Definitions in Guidelines and Expert Panel Ties to Industry: A Cross-sectional Study of Common Conditions in the United States”. This research was driven by concern about the possibility of patients over-diagnosis which might be influenced by any pharmaceutical companies. The interesting part of this article for me is how it criticize guideline making which I never consider of thinking before. After reading the article, rather than debating about conflict of interest which may arise in certain expert panel, I am more concern of the possibility of us, physician, harming our patients while we were using the old diagnosis and treatment approach in the past. For example, some years ago the selected treatment approach for rupture spleen in newborn babies were immediate surgery but since 2004 when a paper about non-surgical treatment was published, non-surgery has been thought as the best treatment option. Surgery in spleen rupture newborn is now considered has more risks than benefits.
A new approach of treating hypovolemic shock, known as hypotensive resuscitation, is the opposite of the common belief  which treats shock patients by administrating massive fluid until the patients reach normal blood pressure. However, in hypotensive resuscitation, loading too much fluid is considered to lessen the hemostatic function since high blood pressure may release the blood clot.
Medicine is one dynamic science that keeps evolving. What we know today as disease reliever might be categorized as harm in the future. Thus, we can never be too confident in treating our patients. When we treat our patients based on medical science today, it’s nothing that we should be proud of because we never know if it will continue to be considered as a definite treatment.